Many diagnostic medical procedures require radiation sources that are introduced into a tissue or ingested by the patient. Such radiation sources preferably have a lifetime of a few hours—enough time to complete the diagnosis, but short enough that damage to tissue from the radiation is avoided and the radioisotope does not decay. Such radiation sources are preferably not chemically poisonous 5′-radio-halogenated-2′-deoxyuridine labeled with radioactive isotopes is such a radiation source. Specifically, iododeoxyuridine labeled with radioisotopes of iodine (“radioiodine”) is such a radiation source.
The lifetime of radioactive isotopes of halogens varies from minutes to days. Radiohalogens are not chemically poisonous in tracer quantities. Radioactive isotopes of halogens have therefore found many uses in making medical and radiopharmaceutical products. One such product is iododeoxyuridine labeled with radioisotopes of iodine. One potential important use is the treatment of neoplastic meningitis with methotrexate and 5-[125I]iodo-2′-deoxyuridine (125IudR). Iododeoxyuridine labeled with radioisotopes of iodine may also prove to be significant therapy for cancer. See, e.g., U.S. Pat. No. 5,077,034, hereby incorporated by reference. Additional uses may include treatment of colorectal tumors, lung tumors and arteriolosclerosis.
Radiohalogenated steroids and proteins can be used to image binding sites for these molecules in a subject or in in vitro assays of binding of such ligands to their receptors.
Several methods are used to label compounds with radiohalogens. These methods are limited by the amount of product they produce and the chemical purity and stability of the compound produced. An additional limitation is the time required to produce the compound must be compatible with the short life of some radioisotopes.
Technical and economic considerations are critical factors in choosing a method for the production of radio-halogenated compounds. Accordingly, a better, more efficient and less costly method of producing radio-halogenated compounds, such as steroids, proteins or nucleotides and nucleosides, for example, iododeoxyuridine labeled with radioisotopes of iodine is needed.
The present invention for large-scale production is simplified, rapid, produces higher yields, can be scaled up and provides an increase in stability of the radio-labeled compound. Typical procedures produce quantities of the scale 50 to 500 micro Ci. This novel method can produce batches of 100 milli Ci to 1 Ci in less time than the methods of the prior art. Specific activities of 1000 to 3000 Ci/mmol can be achieved in the product for labeled nucleoside, nucleotide or derivatives thereof or for labeled steroid products. Specific activities of from 10 to 40 mCi/nanogram can be achieved for labeled protein or labeled peptide products.